WO2022152734A1 - Method and system for producing microstructures - Google Patents
Method and system for producing microstructures Download PDFInfo
- Publication number
- WO2022152734A1 WO2022152734A1 PCT/EP2022/050510 EP2022050510W WO2022152734A1 WO 2022152734 A1 WO2022152734 A1 WO 2022152734A1 EP 2022050510 W EP2022050510 W EP 2022050510W WO 2022152734 A1 WO2022152734 A1 WO 2022152734A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formulation
- opening
- mold
- mold opening
- shaped element
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 44
- 238000009472 formulation Methods 0.000 claims abstract description 136
- 239000000203 mixture Substances 0.000 claims abstract description 136
- 238000004519 manufacturing process Methods 0.000 claims abstract description 24
- 239000010408 film Substances 0.000 claims description 30
- 230000006835 compression Effects 0.000 claims description 29
- 238000007906 compression Methods 0.000 claims description 29
- 238000005452 bending Methods 0.000 claims description 22
- 238000002493 microarray Methods 0.000 claims description 10
- 238000003825 pressing Methods 0.000 claims description 10
- 238000004806 packaging method and process Methods 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000013039 cover film Substances 0.000 claims description 2
- 239000000835 fiber Substances 0.000 description 16
- 238000001035 drying Methods 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- 239000007788 liquid Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 238000007493 shaping process Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000037368 penetrate the skin Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000005096 rolling process Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 230000005489 elastic deformation Effects 0.000 description 1
- 238000004049 embossing Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229920005644 polyethylene terephthalate glycol copolymer Polymers 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/32—Component parts, details or accessories; Auxiliary operations
- B29C43/56—Compression moulding under special conditions, e.g. vacuum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C33/00—Moulds or cores; Details thereof or accessories therefor
- B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
- B29C33/40—Plastics, e.g. foam or rubber
- B29C33/405—Elastomers, e.g. rubber
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C39/00—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor
- B29C39/22—Component parts, details or accessories; Auxiliary operations
- B29C39/24—Feeding the material into the mould
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C39/00—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor
- B29C39/22—Component parts, details or accessories; Auxiliary operations
- B29C39/42—Casting under special conditions, e.g. vacuum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/22—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of indefinite length
- B29C43/222—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of indefinite length characterised by the shape of the surface
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/32—Component parts, details or accessories; Auxiliary operations
- B29C43/34—Feeding the material to the mould or the compression means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/32—Component parts, details or accessories; Auxiliary operations
- B29C43/44—Compression means for making articles of indefinite length
- B29C43/46—Rollers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/32—Component parts, details or accessories; Auxiliary operations
- B29C43/34—Feeding the material to the mould or the compression means
- B29C2043/3483—Feeding the material to the mould or the compression means using band or film carriers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/32—Component parts, details or accessories; Auxiliary operations
- B29C43/56—Compression moulding under special conditions, e.g. vacuum
- B29C2043/561—Compression moulding under special conditions, e.g. vacuum under vacuum conditions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/22—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of indefinite length
- B29C43/28—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of indefinite length incorporating preformed parts or layers, e.g. compression moulding around inserts or for coating articles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2867/00—Use of polyesters or derivatives thereof as mould material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2869/00—Use of PC, i.e. polycarbonates or derivatives thereof as mould material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2875/00—Use of PU, i.e. polyureas or polyurethanes or derivatives thereof, as mould material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
- B29L2031/00—Other particular articles
- B29L2031/753—Medical equipment; Accessories therefor
- B29L2031/7544—Injection needles, syringes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
- B29L2031/00—Other particular articles
- B29L2031/756—Microarticles, nanoarticles
Definitions
- the invention relates to a method for producing microstructures, in particular a method for producing microarrays. Furthermore, the invention relates to a system for producing microstructures, in particular a system for producing microarrays.
- Microarrays have a large number of microneedles, which are usually arranged in or connected to a carrier element, such as in a patch, a plaster or the like.
- the length of the microneedles is in particular dimensioned such that when they are pressed into the skin of a patient, they penetrate the skin only far enough so that nerves and vessels are not touched by the needle tips as far as possible.
- the needles contain an active substance, for example a drug.
- the corresponding active substance can be applied to an upper side of the needle or can be arranged in the needles.
- the needles or parts of the needles are made of a material that dissolves in the patient's skin.
- Microarrays are produced, for example, with the aid of silicone molds which have a large number of mold openings.
- a liquid containing the active ingredient is usually applied to the top of the silicone matrix. After the liquid has dried, another liquid is applied if necessary.
- the carrier element is applied to the underside of the material placed in the silicone matrix, the microneedles are removed from the silicone matrix and then packaged.
- microarrays are currently very complex and expensive. Furthermore, problems arise when filling the mold openings, which are usually conical or pyramid-shaped.
- the mold openings are often not sufficiently filled with filling material. For example, cavities and/or air pockets can occur. This problem occurs in particular in the tips of the mold openings, in particular conical or pyramidal ones. Such incorrect filling can cause problems with the application, for example, since e.g. B. the defective tips do not penetrate the skin properly and/or there may be poor drug dosing due to the lack of formulation in the cavities.
- the object of the invention is to create a method for producing microstructures, in particular microarrays, in which the scalability is improved and which is preferably suitable for the production of large numbers. Furthermore, it is the object of the invention to create a corresponding system for the production of microstructures.
- the object is achieved according to the invention by a method according to claim 1 or a system according to claim 18.
- the method according to the invention for producing microstructures is in particular a method for producing microarrays.
- a preferably first step of the method consists in providing a preferably flat shaped element.
- the mold element has at least one, preferably several, mold openings for the microstructures to be produced.
- the at least one mold opening is in particular a negative mold for the microstructures to be produced.
- the mold opening corresponds in particular to a cavity.
- the at least one mold opening has a first opening and a second opening, in particular opposite the first opening. It is therefore preferred that the mold opening is open on both sides. It is preferable that the first opening and the second opening open the mold opening to the outside.
- a fluid connection between the mold opening and the environment is preferably established through the first opening and the second opening.
- the mold opening preferably runs from one side of the planar mold element to a side of the mold element opposite the first side. If the shaped element is designed as a film in a preferred embodiment, the shaped opening runs in particular from one side of the film to the other side of the film. It is preferred that the at least one mold opening is an embossed mold opening, preferably produced by means of an embossing roller. Another step of the method is providing a first formulation at the second opening. It is preferred that the first formulation has at least one active ingredient. The first formulation is designed in particular to shape tips of the microstructures. The first formulation is provided in particular in such a way that the formulation is in contact with the second opening.
- a further step of the method consists in creating a negative pressure and/or suction in the mold opening.
- the negative pressure can in particular also be referred to as a vacuum, which is preferably not complete.
- negative means in particular a negative pressure ratio compared to the ambient pressure.
- a further, in particular next, step of the method consists in receiving the first formulation through the second opening in the mold opening. The picking up takes place at least partially due to the negative pressure in the mold opening. It is preferred here that the first formulation is sucked in through the second opening. In addition to vacuum pickup of the first formulation, it is preferred to have capillary pickup of the first formulation into the mold opening.
- this absorption by means of capillary action takes place before and/or during of recording by means of negative pressure.
- the first formulation is received in the mold opening in particular to form part of the microstructures to be produced.
- the absorption is in particular a drawing in or sucking in.
- the negative pressure is generated in the mold opening by expanding a volume of the mold opening.
- the volume to be expanded is in particular the volume between the first and the second opening of the mold opening. It is preferred that the expansion of the volume of the mold opening takes place in such a way that the resulting increase in volume essentially corresponds to the volume to be taken up of the first formulation.
- the volume of the mold opening is expanded by at least 3%, preferably by at least 5%, particularly preferably by at least 10%, with more preferably the volume of the mold opening being expanded by at least 20%.
- a further step of the method preferably consists in reducing the volume of the mold opening, this step being carried out before the negative pressure is generated in the mold opening, in particular before the volume of the mold opening is expanded.
- the step of providing the first formulation preferably occurs before and/or after reducing the volume. It is preferred that the volume of the mold opening is reduced in such a way that the resulting reduction in volume essentially corresponds to the volume of the first formulation to be taken up. In particular, the volume of the mold opening is reduced by at least 3%, preferably by at least 5%, particularly preferably by at least 10%, with the volume of the mold opening more preferably being reduced by at least 20%. It is preferred that the volume of the mold opening is reduced by at least partially compressing the mold element. Compression is in particular pressing and/or longitudinal stretching. For compression, it is preferred that the shaped element is pressed on the side of the first opening, preferably on both sides of the two openings, and/or the shaped element is stretched, in particular in the longitudinal direction.
- the shaped element is compressed by means of at least one roller.
- the roller is in particular a press roller.
- the at least one press roller presses on at least one surface, in particular on the surface of the first opening of the shaped element.
- the compression is particularly preferably carried out by means of two rollers on both sides of the shaped element. It is preferred that the two rolls are offset in the rolling direction.
- a further step of the method preferably consists in arranging an auxiliary element on the side of the shaped element which has the first opening.
- the auxiliary element is brought into contact with this side, in particular connected to it, preferably adhesively.
- the auxiliary element preferably has an auxiliary film, in particular consists of it.
- the auxiliary element is preferably arranged before the negative pressure is generated in the mold opening, particularly preferably before the volume of the mold opening is expanded.
- the auxiliary element is arranged before or during the reduction of the volume of the mold opening.
- a further step of the method preferably consists in closing the first opening of the mold opening.
- the first opening is sealed in an essentially airtight manner. It is preferred that the closing takes place with the auxiliary element, so that the auxiliary element seals the first opening of the mold opening.
- the step of closing the first opening occurs before the negative pressure is created in the mold opening. In particular, this is done closing the first opening after reducing the volume of the mold opening, preferably after compressing the mold element.
- a preferred further step of the method consists in removing the auxiliary element, preferably from the mold element. This removal occurs after the first formulation has been received in the mold opening. It is preferred that the removal takes place by pulling off the auxiliary element.
- the at least one mold opening is cylindrical or conical.
- the cylindrical or conical shape has in particular a round, triangular or quadrangular, particularly preferably square, cross section. It is preferred that the cone shape tapers from the first opening to the second opening of the mold opening. It is possible that the cone shape is designed as a truncated cone. A cone shape with an angular cross-section can also be described as a pyramid shape.
- the second opening preferably has a smaller cross-sectional area than the first opening.
- the cross section of the mold opening preferably tapers from the first opening towards the second opening.
- the volume of the mold opening is reduced, in particular the at least partial compression of the mold element, by bending the mold element.
- the bending takes place in particular along a transverse direction of the shaped element, so that in particular a bending edge is perpendicular to the longitudinal direction of the shaped element.
- the bending takes place in the direction of the first opening and/or in a direction opposite to the direction of the narrowing of the mold opening, in particular in the case of a conical mold opening.
- a compressed fiber of the mold element is preferably located on the side of the first opening and/or on the side on which the mold opening is enlarged.
- the bending takes place in particular at an angle of from 0° to 180°, preferably from 10° to 90°, particularly preferably from 30° to 60°.
- the shaped element has, in particular, a neutral fiber and a compressed fiber on the side of the shaped element into which the bending takes place, and a stretched fiber on the side opposite the compressed fiber.
- the compressed area, in particular the compressed fiber, of the shaped element is preferably reduced.
- the mold opening preferably the volume of the mold opening, is also reduced in this area of the mold element.
- the bending preferably causes the stretched area, in particular the stretched fiber, of the shaped element to increase.
- the mold opening preferably the volume of the mold opening, also increases in this area of the mold element.
- the mold opening has a larger volume on the compressed fiber side, in particular significantly, than on the side with the stretched fiber.
- the volume on the side of the compressed fiber decreases more than the volume on the side of the stretched fiber increases.
- the bending preferably takes place with the at least one roller.
- the at least one roller is then preferably a bending roller.
- the volume is expanded in particular by moving the shaped element back, in particular to its original shape.
- the setting back is particularly preferably a reverse bending of the shaped element bent by the bending and/or a relaxation of the compressed, in particular pressed and/or longitudinally stretched shaped element. It is preferred that the shaped element has a film, in particular consists of it.
- the molded element has TPU, PC or PETG, in particular consists of them.
- the shaped element is preferably compressible. It is preferred that the shaped element is designed to be elastic.
- a second formulation is preferably provided at the first opening. It is preferred that the second formulation is drug-free. However, it is also possible for the second formulation to have at least one active ingredient.
- the second formulation is taken up through the first opening into the mold opening. It is preferred that the mold opening, in particular the remaining volume of the mold opening, is completely filled with the second formulation.
- the second formulation combines with the first formulation, preferably in a materially bonded manner.
- the second formulation is preferably picked up by being pressed in, in particular pressed in. The pressing is preferably carried out by means of a roller.
- the formulation in contact with the first opening on one side and is covered on the other side by a formulation element, in particular the second formulation element described below.
- the pressure for pressing in the second formulation, in particular the roller, is preferably applied to this formulation element.
- the first formulation is preferably provided by means of a first formulation element.
- the first formulation element preferably has a film, in particular consists of it.
- the first formulation element has the first formulation.
- the first formulation is preferably arranged, in particular in droplets, on the first formulation element.
- the first formulation element has a formulation receptacle, preferably one that has a recess.
- this formulation receptacle is a kind of bowl-shaped form in the formulation element, in which the formulation is located.
- the second formulation is provided by means of a second formulation element which has the second formulation.
- the second formulation element is designed correspondingly with one or more features of the first formulation element.
- drying takes place in particular.
- the drying of the first and/or second formulation takes place in particular through the first opening of the mold opening.
- the drying takes place in particular by means of a preferably warm air stream, which in particular has direct contact with the first and/or the second formulation. It is preferred that drying causes the first and/or second formulation to solidify into microstructures.
- drying can be carried out by means of thermal radiation, in particular infrared radiation.
- a preferred further step of the method consists in a, in particular metrological, testing of the first and/or second formulation.
- the testing is carried out in particular by means of an optical testing device. It is preferred that the optical inspection device has a camera. Testing occurs after picking up the first and/or after picking up the second formulation. It is particularly preferred that the testing takes place after or before the drying step.
- the first formulation, which has at least partially solidified into the microstructure, and preferably the second formulation connected to the first formulation, are preferably removed from the mold. Demolding occurs at and through the first opening of the mold opening. Demoulding preferably takes place after drying, particularly preferably after testing. Demolding preferably occurs on the second formulation.
- the demoulding is preferably carried out by means of a cover element.
- the cover element has in particular a cover film, in particular consists of it.
- the cover member is bonded to the first formulation or the second formulation. It is preferred that the connection is materially bonded, in particular adhesive.
- demoulding is carried out by removing, in particular pulling off, the mold element. It is preferred that the cover element is the second formulation element, so that demolding takes place by means of the second formulation element.
- the microstructure that has been removed from the mold is preferably packaged. It is preferred that the packaging takes place by means of a blister element. Packaging is particularly preferably carried out using blister film.
- the method is carried out with a system having one or more features of the system described below.
- the system according to the invention for producing microstructures is in particular a system for producing microarrays.
- the system is in particular a device.
- the system is preferably designed to carry out the method described above. It is particularly preferred that the system has one or more of the features described above, in particular the device features described there.
- the system has a feature.
- the form element is in particular compressible or elastic.
- the mold element has at least one mold opening for the microstructures to be produced.
- the at least one mold opening is in particular a negative mold for the microstructures to be produced.
- the mold opening corresponds in particular to a cavity.
- the mold opening preferably has a first opening and a second opening, in particular opposite the first opening.
- the mold opening is in particular open on both sides, so that the mold element has at least one continuous mold opening.
- the first opening and the second opening open the mold opening to the outside.
- a fluid connection between the mold opening and the environment is preferably established through the first opening and the second opening.
- the system also has a compression device.
- the compression device is in particular a pressing and/or bending device.
- the compression device preferably has a roller, particularly preferably a press roller and/or bending roller, and in particular consists of it.
- the compression device is designed to compress the shaped element.
- the compression device is arranged and/or designed for a pressing action on the shaped element and/or for bending the shaped element.
- the compression device is designed to reduce the volume of the mold opening by compression.
- the compression device has two opposite rollers, in particular press rollers and/or bending rollers.
- the rollers are in particular arranged in such a way that the shaped element can be compressed between the rollers, in particular can be pressed and/or bent.
- the forming element is preferably located between the rollers. In particular, the rollers are offset in relation to one another and/or in the roller feed direction.
- the system comprises an isolator, preferably aseptic, in which at least the compression device and at least part of the mold element are arranged.
- the shaped element of the method according to the invention and/or the system according to the invention is in particular a shaped element according to DE 10 2020 125 484 A1.
- FIG. lb also showing an embodiment of a system for the production of microstructures according to the invention
- FIG. 2a-2c schematic, sectional side views of production states to illustrate the method according to the invention, with FIG. 2c also showing an embodiment of a system for the production of microstructures according to the invention
- FIG. 3 shows a schematic, sectional side view of a production state to illustrate the method according to the invention, wherein an embodiment of a system for the production of microstructures according to the invention is also shown,
- FIG. 4 shows a schematic, sectional side view of a manufacturing state for showing an embodiment of the method according to the invention.
- FIG. 5 shows a schematic side view to illustrate an embodiment of the method according to the invention with an illustration a further embodiment according to the invention of a system for the production of microstructures.
- FIG. 1a shows a shaped element 10, which is designed here in particular as an elastic film 11.
- the film 11 has a first side 16 and a second side 20 opposite.
- Conical or pyramidal shaped openings 12 run through the film 11 .
- the shaped openings 12 have a first opening 14 on the first side 16 .
- the mold openings 12 taper, starting from the first side 16 to the second side 20, with a second opening 18 being formed on the second side 20.
- a first formulation 22 preferably containing an active substance, is arranged on the second side 20 in contact with the second openings 18 of the mold openings 12 . It is possible (not shown) that part of the formulation 22 is taken up into the mold openings 12 through the second openings 18 due to capillary effects.
- Arrow 52 shows an infeed and arrow 54 shows a discharge of the mold element, so that the method can preferably be carried out as a flow process and/or as a roller process.
- Fig. Lb shows a second state of the embodiment of Fig. La.
- a pressure has been exerted on the shaped element 10 or the film 11.
- the mold element has preferably been compressed. Due to the exertion of pressure, the mold element 10 is compressed, so that the volume of the mold openings 12′ compared to the leadership from Fig. La was reduced.
- the pressure can be exerted by means of a compression device 37, for example a pressing device or a rolling device, on one side or on both sides of the shaped element 10.
- FIG. 1b Also shown in FIG. 1b is a system 100 for producing microstructures with a shaped element 10 and a compression device 37.
- This compression device 37 is, in particular, a pressing device.
- Fig. Lc shows another state based on the statements from Figures la and lb.
- an auxiliary element 26 in particular designed as a film, was arranged on the first side 16 of the shaped element 10.
- the auxiliary element 26 closes the first openings 14 of the volume-reduced mold openings 12'.
- Fig. Id shows another state of the statements from Figures la to lc.
- the shaped element 10 has stretched back elastically.
- the volume of the mold openings 12 has expanded again.
- the expansion of the volume of the mold openings 12 creates a negative pressure in the mold openings 12.
- the first opening 14 of the mold openings 12 is closed, suction occurs at the second openings 18.
- the first formulation was taken up, in particular sucked in, by the suction 22 into the mold openings 12 so that the mold openings 12 are now partially filled with formulations 22'. It is also possible that the entire mold openings 12 are filled with the first formulation 22 by appropriate dimensioning.
- the shaped element 10 from FIG. 2a essentially corresponds to the shaped element 10 from FIGS.
- the first formulation 22 takes place in a depression 32 of a formulation element 30 designed as a film 30.
- the depression 32 is here on a first side 34 of the formulation element 30, it being preferred for the depression 32 to essentially correspond to a negative shape of the projection 36.
- FIG 2a shows that the film 11 of the shaping element 10 and the film 30 of the formulation element 30 are brought together, in particular connected (joining shown from left to right).
- FIG. 2b shows a further state according to the embodiment from FIG. 2a.
- Forming element 10 and formulation element 30 are connected to one another here, so that projection 36 is arranged in recess 32 .
- a portion of the formulation 22 has entered the tips 42 of the mold openings 12 through second openings 18 due to capillary effects.
- FIG. 2c shows a further state, it being preferable for the embodiment from FIG. 2b to be fed in from the left in the direction of arrow 52 .
- the compression device 37 which has two offset rollers 38, 40 here, exerts pressure or compresses the shaped element 10 (represented by arrows 23') - the shaped element with the formulation element 30 connected thereto runs from left to right (in the direction of the arrows 52, 54).
- the direction of rotation of the rollers 38, 40 is represented by arrows 56. It is shown preferred that roller 38 rotates clockwise and roller 40 rotates counterclockwise. Due to the pressure exerted by the rollers 38, 40 on the mold element 10 (corresponding to arrows 23 ') and A longitudinal expansion, in particular due to the tensile force of the rollers 38, 40, results in a compression of the elastic mold element 10. Due to this compression, the volume of the mold openings 12 of the mold element 10 decreases.
- the mold element has already been compressed in the area of the mold opening 12", so that the volume of the mold opening 12" is reduced.
- the mold element 10 has not yet been compressed, so that the volume of the mold openings 12' is in the initial state.
- auxiliary element 26 designed as a film is shown being fed in the direction of arrow 58 in the region between the rollers 38 , 40 .
- the auxiliary element 26 in this case covers the first side 16 of the compressed mold element 10, so that the first openings 14'' of the reduced-volume mold openings 12'' are closed.
- the shaped element relaxes, preferably stretches back elastically. This is shown in area B. Due to the elastic deformation of the mold element 10, the volume of the mold openings 12 expands. This results in a negative pressure in the mold openings 12. The negative pressure causes the first formulation 22 to be sucked in through the second openings 18 of the mold openings 12.
- the mold opening 12 shown on the right “" has already expanded completely here, so that part of the mold openings 12"" is already completely filled with the first formulation 22"".
- the volume of the mold openings 12 ′′′ on the other hand, has not yet been completely expanded, so that part of the formulation 22 ′′′ was first taken up, while part of the formulation 22 ′ remains in the depression 32 .
- this subsystem 101 for producing microstructures with a compression device 37, shaping element 10, auxiliary element 26 and formulation element 30.
- the compression device 37 is in particular a pressing device.
- this subsystem 101 corresponds to an embodiment according to the invention of a system 100 for the production of microstructures.
- FIG. 3 also shows a manufacturing state, it being preferable for the embodiment from FIG. 2b to be supplied from the left in the direction of arrow 52 .
- the embodiment of FIG. 3 was in particular an alternative to the embodiment of FIG. 2c.
- the representation of FIG. 3 is based on the representation of FIG. 2c.
- Compression device 37 which here has two offset rollers 38, 40, bends shaped element 10 about roller 40.
- the shaped element with formulation element 30 connected thereto runs from left to right (in the direction of arrows 52, 54).
- the direction of rotation of the rollers 38, 40 is represented by arrows 56. It is shown preferred that roller 38 rotates clockwise and roller 40 rotates counterclockwise. Due to the bending of the shaped element 10 (shown in area B'), there is a compressed area 72, also referred to as a compressed fiber, and a stretched area 74, also referred to as a stretched fiber, of the shaped element 10 on both sides of the neutral fiber 70 .
- the compression results in a reduction in the volume 13' in the compressed area of the mold opening 12".
- the stretched area of the mold opening 12 on the other hand, there is an increase in the volume 13". Since the volume proportion of the compressed area , is significantly larger in comparison to the part that lies in the stretched area, there is a total reduction in volume of the mold opening 12".
- the shaped element 10 has not (yet) been bent, so that the volume of the shaped openings 12' is (still) in the initial state.
- auxiliary element 26 designed as a film is shown being fed in the direction of arrow 58 in the region between the rollers 38 , 40 .
- the auxiliary element 26 in this case covers the first side 16 of the compressed mold element 10, so that the first openings 14'' of the reduced-volume mold openings 12'' are closed.
- the shaped element 10 After passing through the area between the rollers 38, 40, the shaped element 10 is returned to the initial, non-bent, state. This now results in a total volume increase of the mold opening, which is the opposite of the total volume reduction in area B′. This results in a negative pressure in the mold openings 12. The negative pressure causes the first formulation 22 to be sucked in through the second openings 18 of the mold openings 12.
- FIG. 3 Also shown in FIG. 3 is a subsystem 101 for producing microstructures with a compression device 37, shaping element 10, auxiliary element 26 and formulation element 30.
- This compression device 37 is, in particular, a bending device.
- this subsystem 101 corresponds to an embodiment according to the invention of a system 100 for the production of microstructures.
- a shaped element 10 is fed in from the left in the direction of arrow 52 .
- the mold element 10 has a plurality of mold openings 12 .
- the underside of the mold element 10 is connected to a formulation element 30 .
- the shaped element 10 is designed in accordance with the explanations in FIGS.
- the mold openings 12' are already partially filled with a first formulation 22', but the region of the pyramid base of the mold openings 12' is empty.
- a formulation 50 preferably free of active ingredient, was applied to the shaped element.
- a second formulation element 116 which is designed in particular as a film, is supplied, which covers the second formulation. Pressure is exerted on the second formulation element 116 via the roller 110 so that a pressing connection of the second formulation element 116 to the mold element 10 takes place. This forces the second formulation 50 into the empty areas of the mold openings 12'.
- the mold openings 12'' are thus filled with the second formulation 50'.
- the entire mold openings 12 are therefore filled with formulations which, in particular after curing, correspond to microstructures.
- FIG. 4 shows a subsystem 103 of a system 100 for producing microstructures.
- FIG 5 shows an embodiment of a system 100 according to the invention for the production of microstructures.
- the system 100 is arranged in a housing 102 .
- the housing is preferably sterile from the environment. Supplied elements are preferably sterilized before being supplied and/or are guided into the housing 102 through mouse holes.
- the housing 102 is in particular an insulator.
- the films are preferably fed into the system using a packaging tube.
- a first formulation element 30 is fed in the direction of arrow 52', in particular by means of a packaging tube 31.
- An auxiliary element 26, preferably in the form of a film, is fed in the direction of arrow 58.
- the auxiliary element 26 is fed in in particular in a packaging tube 47.
- the area shown in box IIc is designed in particular in accordance with the embodiment from FIG. 2c or FIG. 3 .
- the first formulation 22 is provided via a first formulation dispenser 21 which applies the formulation 22 as droplets 22 ′ to the formulation element 30 , in particular in depressions 32 of the formulation element 30 .
- the auxiliary element 26 is preferably removed via rollers 108.
- the first formulation 22 is then preferably dried in the mold element 10′ via the drying device 104a.
- testing of the shaped element 10" is preferably followed by testing of the shaped element 10", in particular the preferably solidified formulation 22.
- the testing is preferably carried out using a testing device 106a.
- the testing device is in particular optical.
- the testing device particularly preferably has at least one camera.
- the adjoining area III is preferably designed as shown in FIG.
- the second formulation 50 is provided in particular by means of a second formulation dispenser 51, which applies the formulation 50 as droplets 50' to the shaped element 10''".
- the second formulation element 60 is used in particular as part of a packaging hose 118 performed.
- the second formulation element 60 has in particular a permeable and/or moisture-absorbing film, in particular consists of it.
- the shaped element 10 is preferably removed via rollers 114. It is particularly preferred here that the first formulation element 30 is also removed. However, it is also possible for the first formulation element 30 to be discharged beforehand, at some point after region IIc.
- the formulations 22, 50 which are preferably connected to microstructures 120, are removed from the mold. It is preferred here that the microstructures 120 are connected, for example adhesively, to the second formulation element and the microstructures 120 are therefore removed from the mold and continued.
- the preferably connected formulations 22, 50 which correspond to the microstructures 120 to be produced, are preferably dried.
- the drying can take place by means of a drying device 104b. Additionally or alternatively, however, air drying can also take place through the preferably permeable and/or moisture-absorbing film 60 .
- the microstructures 120 are preferably tested. It is preferred that the testing is performed using a testing device 106b.
- the testing device has at least one camera.
- the microstructures 120 are then preferably packaged.
- a blister film 122 is preferably fed in the direction of the arrow 62 .
- the supply takes place in particular along rollers 126, 128.
- the blister film 122 has a plurality of blisters 123 which are open at the top.
- the blister film 128 is connected to the microstructures 120.
- the microstructures 120 are received in the blisters 123, so that blister-packed microstructures 124 are present. These are discharged in the direction of arrow 54.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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CA3200921A CA3200921A1 (en) | 2021-01-12 | 2022-01-12 | Method and system for producing microstructures |
CN202280008400.XA CN116635201A (en) | 2021-01-12 | 2022-01-12 | Method and system for producing microstructures |
US18/271,756 US20240058995A1 (en) | 2021-01-12 | 2022-01-12 | Method and System for Producing Microstructures |
EP22702152.4A EP4277776A1 (en) | 2021-01-12 | 2022-01-12 | Method and system for producing microstructures |
JP2023542627A JP2024505414A (en) | 2021-01-12 | 2022-01-12 | Method and system for manufacturing microstructures |
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DE102021100396.2 | 2021-01-12 | ||
DE102021100396.2A DE102021100396A1 (en) | 2021-01-12 | 2021-01-12 | Process and system for the production of microstructures |
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WO2022152734A1 true WO2022152734A1 (en) | 2022-07-21 |
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PCT/EP2022/050510 WO2022152734A1 (en) | 2021-01-12 | 2022-01-12 | Method and system for producing microstructures |
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US (1) | US20240058995A1 (en) |
EP (1) | EP4277776A1 (en) |
JP (1) | JP2024505414A (en) |
CN (1) | CN116635201A (en) |
CA (1) | CA3200921A1 (en) |
DE (1) | DE102021100396A1 (en) |
WO (1) | WO2022152734A1 (en) |
Citations (8)
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EP2343101A1 (en) * | 2009-10-08 | 2011-07-13 | BioSerenTach Co., Ltd. | Stamper for microneedle sheet, method for manufacturing the stamper, and method for manufacturing microneedle using the stamper |
KR20170011578A (en) * | 2015-07-23 | 2017-02-02 | 주식회사 엔이케이 | Microneedle manufacturing system for transdermal delivery |
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WO2018213605A1 (en) * | 2017-05-17 | 2018-11-22 | University Medical Pharmaceuticals Corp. | System and method for manufacturing microneedle devices |
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DE102005042656A1 (en) | 2005-09-08 | 2007-03-15 | Robert Bosch Gmbh | Micromechanical micro pump for dosing medicine, has substrates connected with each other by anodic bonds, where one substrate is made up of silicone and includes unstructured side and connected with other substrate at unstructured side |
DE102011054789A1 (en) | 2011-10-25 | 2013-04-25 | Universität Kassel | Nano-shape structure |
DE102018009594A1 (en) | 2018-12-11 | 2020-06-18 | Lts Lohmann Therapie-Systeme Ag | Method and device for producing microneedles |
DE102020125484A1 (en) | 2020-09-30 | 2022-03-31 | Lts Lohmann Therapie-Systeme Ag | Process for producing a shaped element for the production of microarrays and shaped element |
-
2021
- 2021-01-12 DE DE102021100396.2A patent/DE102021100396A1/en active Pending
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2022
- 2022-01-12 CA CA3200921A patent/CA3200921A1/en active Pending
- 2022-01-12 JP JP2023542627A patent/JP2024505414A/en active Pending
- 2022-01-12 US US18/271,756 patent/US20240058995A1/en active Pending
- 2022-01-12 EP EP22702152.4A patent/EP4277776A1/en active Pending
- 2022-01-12 WO PCT/EP2022/050510 patent/WO2022152734A1/en active Application Filing
- 2022-01-12 CN CN202280008400.XA patent/CN116635201A/en active Pending
Patent Citations (8)
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EP2343101A1 (en) * | 2009-10-08 | 2011-07-13 | BioSerenTach Co., Ltd. | Stamper for microneedle sheet, method for manufacturing the stamper, and method for manufacturing microneedle using the stamper |
US20170050010A1 (en) * | 2014-04-24 | 2017-02-23 | Georgia Tech Research Corporation | Microneedles and Methods of Manufacture Thereof |
EP3144030A1 (en) * | 2014-05-15 | 2017-03-22 | Fujifilm Corporation | Transdermal absorption sheet and method of manufacturing transdermal absorption sheet |
KR20170011578A (en) * | 2015-07-23 | 2017-02-02 | 주식회사 엔이케이 | Microneedle manufacturing system for transdermal delivery |
US20200197679A1 (en) * | 2015-12-24 | 2020-06-25 | Guangzhou Neworld Micnanobio Pharmatech Co., Ltd. | Microneedle chip and manufacturing method |
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WO2018213605A1 (en) * | 2017-05-17 | 2018-11-22 | University Medical Pharmaceuticals Corp. | System and method for manufacturing microneedle devices |
US20190351204A1 (en) * | 2018-05-16 | 2019-11-21 | Fujifilm Corporation | Method of manufacturing microneedle array |
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DE102021100396A1 (en) | 2022-07-14 |
CA3200921A1 (en) | 2022-07-21 |
CN116635201A (en) | 2023-08-22 |
EP4277776A1 (en) | 2023-11-22 |
US20240058995A1 (en) | 2024-02-22 |
JP2024505414A (en) | 2024-02-06 |
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